Learn more about the research interests of our current EITS students by selecting their name below.
Cooperating Doctoral Program: Biochemistry and Molecular Biology
EITS Track: Biomedical Toxicology
Education: Bachelor of Medicine, Bachelor of Surgery, Rajshahi University, Bangladesh
Research Interests:
My research interest focuses on elucidating the relationship between cholesterol and glucose homeostasis in TCDD-induced toxicity. Previous research from the LaPres and Zacherewski labs have demonstrated that mice given a 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) inhibitor (i.e. statin) display markers of increased TCDD-induced toxicity compared to TCDD alone. My research is focused on mechanistically linking changes in statin-induced changes in cholesterol homeostasis and the observed pathology induced by TCDD. To accomplish this goal, I will use in vivo models, both wild type and tissue-specific AHR knockout mice, and the human hepatocyte cell line, HepaRG.
Major Professor: John LaPres, Biochemistry and Molecular Biology
Contact: arajesmi@msu.edu
Cooperating Doctoral Program: Cell and Molecular Biology
EITS Track: Biomedical Toxicology
Education: B.S. Cell and Molecular Biology, Grand Valley State University
Research Interests:
My proposed doctoral research includes (1) the utilization of mouse thermoneutral studies to assess the progression of toxicant associated fatty liver disease (TAFLD) with broad implications of human nonalcoholic fatty liver disease (NAFLD) progression. Standard mouse toxicology studies are conducted at human thermoneutral temperatures (20 – 23°C) leading to unwarranted cold stress. By investigating the toxicological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) at 29 – 32°C, the progression of toxicant-induced liver disease is expected to mimic that more closely to human NAFLD pathologies. Work from my doctoral project with will include a collaboration with Dr. Arjun Krishan's lab (Computational Mathematics, Science and Engineering department) to employ (2) the application of contemporary data science techniques to integrate experimental datasets produced from -omic experiments, such as (but not limited to) RNA-seq, ChIP-seq, and metabolomics. Data generated as part of my project will (3) adhere to the implementation of Findable, Accessible, Interoperable, and Reusable (FAIR) guidelines by coordinating with the Data Management and Analysis (DMAC) core. These datasets will be further developed with the web-based application FAIRtox to provide researchers and the public the opportunity to interact with dose-dependent toxicological RNA-seq data, ChIP-seq, and, in the future, other -omic datasets.
Major Professor: Timothy Zacharewski, Biochemistry and Molecular Biology
Contact: sinkwarr@msu.edu
Cooperating Doctoral Program: Biomedical Engineering
EITS Track: Biomedical Toxicology
Education: B.S. Biomedical Engineering, Wright State University
Research Interests:
Orofacial clefts are one of the most common structural birth defects that arise from a complex, multi-factorial etiology. My work focuses on engineering ways to study the complex cell-cell interactions of development and identify potential harmful exposures with a primary focus on the Sonic Hedgehog (SHH) pathway. To accomplish this, I utilize computer numerical control (CNC) machining to create plate based microfluidic devices that create a 3D microtissue of the epithelial-mesenchyme interaction that is essential to proper orofacial development. In parallel with this, I work with the Organization for Economic Cooperation and Development's (OECD) Adverse Outcome Pathway (AOP) program to develop a network of AOPs linking disruption of the SHH signaling pathway with orofacial clefting. Through this work I have identified data gaps that our engineered model will be applied to address. Combining the engineering model with the AOP allows us to fill data gaps of direct regulatory interest. I hope that through this work a more robust risk assessment pipeline can be created that can be used to identify exposures so the incidence of these birth defects can be reduced.
Major Professor: Brian Johnson, Pharmacology and Toxicology, Biomedical Engineering
Contact: reyno538@msu.edu
Cooperating Doctoral Program: Chemistry
EITS Track: Biomedical Toxicology
Education: B.S. Chemistry, B.A. Biology, University of Nebraska at Omaha
Research Interests:
My research interests include studying how endogenous oxidized polyunsaturated fatty acid (PUFA) metabolites, also called oxylipins, affect age-associated neurodegenerative diseases. Throughout this work I will identify and study the corresponding mechanism of oxylipins that either accelerate or alleviate age-associated neurodegeneration, specifically the epoxy- and dihydroxy-metabolites of omega-3 (ω-3) and omega-6 (ω-6) fatty acids.
Endogenous oxylipins are crucial in human and animal physiologies as they are involved in CNS and cardiovascular functions, inflammation, and tissue repair despite their low abundance. As well, recent studies have indicated that chronic metabolic and neurodegenerative diseases could significantly impact the endogenous oxylipin profile in target tissues and inhibiting the metabolism of specific oxylipins could be beneficial to these diseases. In addition, several recent studies show that the exposome, such as a fatty acid diet, environmental toxicants, and everyday products, can impact oxylipin metabolism. Thus, in this specific project, I hypothesize that changes in the oxylipin profiles in C. elegans due to the exposome or aging consequently affect age-associated neurodegeneration. However, investigating the crosstalk between oxylipin metabolism and age-associated neurodegeneration in mammalian models and humans is challenging owing to the length of the experiments and difficulties to control potential exposures that could affect oxylipin metabolism. Therefore, in my thesis project, I propose to conduct our study in the model organism Caenorhabditis elegans (C. elegans) as the neuron signaling and PUFA metabolism of humans are conserved in C. elegans, their transparent body facilitates fluorescence neuronal imaging assays, and their relatively short lifespan expedites aging studies compared to other biological models. As well, C. elegans are genetically malleable and their diet can easily be modified to introduce a variety of compounds or varying fatty acid concentrations.
To test our hypothesis, we will analyze the oxylipin profile in C. elegans exposed to environmental toxicants at different ages to identify the oxylipins that are significantly impacted by exposome or aging. These identified oxylipins will then be supplemented to C. elegans allowing use to subsequently analyze how the exposome and aging affects neurodegeneration in C. elegans with phenotypic and morphological assays. By combining the results from these studies, we could delineate the mechanism behind how the exposome affects aging and age-associated neurodegeneration through PUFA oxylipin signaling pathways.
Here I propose to use state-of-the-art oxylipin profiling and neuronal function assays to i) identify specific metabolic changes in abundance within the oxylipin profiles throughout the lifespan that may be involved in aging, ii) determine the effect (i.e., severity, motor neurons affected, changes in lifespan) of these identified metabolites on neurodegeneration and neurodegeneration recovery, and iii) investigate a possible mechanism of ferroptosis, an iron-dependent programmed cell death that is characterized by an accumulation of lipid reactive oxygen species, to be responsible for the metabolic changes over the lifespan further resulting in the observed neurodegeneration. Once I establish the methodology for my research, and along with the study of oxylipins, I will then investigate how common yet toxic compounds (i.e., pesticides, metals, over-the-counter drugs, and personal care products) can affect aging and neurodegeneration with sustained exposure through the oxylipin signaling pathway. With these projects, I hope to elucidate the mechanism and progression of neurodegeneration due to these differences in fatty acid levels and exposure to environmental toxic chemicals in C. elegans that could translate to neurological diseases in humans, such as Parkinson’s and Alzheimer’s diseases. If these studies exhibit promising results corresponding to a causal effect between oxylipins and neurodegeneration in C. elegans, further studies could be conducted in more sophisticated mammalian models to support these results.
Major Professor: Kin Sing Lee, Pharmacology and Toxicology
Contact: hinmanje@msu.edu
Cooperating Doctoral Program: CMIB
EITS Track: Food Toxicology & Ingredient Safety Track
Education: B.S. Veterinary and Biomedical Science, B.S. Nutrition, Pennsylvania State University, D.V.M. Michigan State University
Research Interests:
As a resident and graduate student in veterinary toxicology, I provide consultation services to veterinarians and pet owners for a variety of toxicology cases including accidental and malicious poisonings, environmental contaminants, and pet food complaints. In this role, I support both consumers and government agencies with testing recommendations and incident reporting to the Food and Drug Administration (FDA) Safety Reporting Portal. My current research efforts focus on testing cannabidiol (CBD) infused pet treats for cannabinoid content against manufacturer label claims. Currently, a federal regulatory pathway for cannabinoids in pet foods, feeds, and "supplements" does not exist. An aim of this dissertation is to establish a quantitative GC-MS/MS method for cannabinoid analysis in feed and treat matrices. My broader research interests include veterinary vitamin and mineral nutrition, nutrition and toxicology diagnostics and method development, wildlife toxicology, and veterinary pharmacology.
Major Professor: John P. Buchweitz, MSU Veterinary Diagnostic Laboratory
Contact: sheffle5@msu.edu
Cooperating Doctoral Program: CMIB
EITS Track: Biomedical Toxicology
Education: Biochemistry and Molecular Biology, Michigan State University
Research Interests:
Both chronic liver disease and acute liver injury can be induced by chemical exposures and in each context, the blood coagulation cascade is activated. Multiple studies suggest that components of the blood coagulation system modify the pathogenesis of acute hepatotoxicity and participate in the regeneration of the injured liver. My research is focused on defining the precise mechanisms linking the clotting protein fibrinogen to liver injury and repair.
After partial liver resection, the remaining liver regenerates, driven in part by hepatocyte proliferation, to restore normal hepatic functions. This surgical procedure is used to remove liver tumors and in the case of living donor liver transplantation. Interestingly, up to 10% of patients develop complications after partial resection. This can extend hospitalization time, and lead to serving complications including liver failure or death. After liver resection (partial hepatectomy, PHx), blood coagulation is activated, and fibrinogen is deposited in the liver. Prior studies suggest that failed hepatic fibrinogen deposition or low plasma fibrinogen after surgery is associated with post-operative liver dysfunction. Moreover, in the 2/3rd partial hepatectomy model in mice, fibrinogen depletion with ancrod significantly reduced hepatocyte proliferation. What’s more, prior studies also suggest the protein that degrades fibrinogen also contributes to hepatocyte proliferation, which further articulates the role of fibrinogen on hepatocyte proliferation. Although prior studies suggest that fibrinogen contributes to liver regeneration after PHx, the precise mechanisms are unclear. This is the focus of my research.
Major Professor: James Luyendyk, Pathobiology and Diagnostic Investigation
Contact: weizimu@msu.edu
Cooperating Doctoral Program: Fisheries & Wildlife
EITS Track: Environmental Toxicology Track
Education: B.S. Fisheries, Central Luzon State University
Research Interests:
My dissertation topic focuses on understanding the impact of emerging pollutants, specifically per- and poly- fluoroalkyl substances (PFAS), on fish health. In particular, my research interests are directed towards a comprehensive investigation of the interplay between PFAS exposure and its subsequent effects on disease susceptibility, disease progression/pathogenesis, immunological responses and overall survivability of prominent Great Lakes fishes including Lake whitefish, Lake trout and Steelhead trout.
Major Professor: Cheryl Murphy, Fisheries & Wildlife
Contact: manlicli@msu.edu
Cooperating Doctoral Program: Fisheries & Wildlife
EITS Track: Environmental Toxicology Track
Education: B.S. Environmental Science & Management, Environmental Studies and Sustainability, Michigan State University
Research Interests:
I am interested in research topics related to:
Major Professor: Cheryl Murphy, Fisheries & Wildlife
Contact: asexton@msu.edu
Cooperating Doctoral Program: Food Science & Human Nutrition
EITS Track: Biomedical Toxicology Track
Education: B.S. Animal Science, Michigan State University
Research Interests:
My research interests center around the intersection between nutrition, toxicology, and pregnancy. I have a particular interest in the relationship between maternal obesity and endocrine disrupting chemicals (EDCs) and their impact on the anogenital distance (AGD) and 2:4 finger digit ratio (2:4D) of the offspring. Obesity is a prominent condition in the United States and an alarming number of women begin pregnancy as obese. This presents problems for the offspring because maternal obesity has been linked to increased risk for development of metabolic diseases and reproductive disorders. In the past, AGD and 2:4D ratios have been used as indicators of reproductive function later in life. The hormonal shifts in testosterone and estrogen resulting from obesity may alter the AGD and 2:4D of offspring, thus potentially providing a window into in-utero development and early biomarkers of reproductive disorders.
EDCs are near impossible to avoid and can be found in personal care products, cosmetics, plastics, and food wrappings. Recent studies with EDCs have shown that AGD and 2:4D reflect the uterine environment and could be useful in understanding the mechanisms and effects of EDCs and EDC alternatives on fetal development and maternal health. Ultimately, I would like to direct my research towards the interaction between hormones, EDCs, and women's health. Pregnancy is a critical period for both the mother and the fetus, but environmental factors- such as diet and chemical exposures- can have profound impact on a woman's health before and after pregnancy. Furthermore, the effects of these EDCs during pregnancy may contribute to the development of uterine fibroids, cardiovascular disease, and other health conditions.
Major Professor: Rita Strakovsky, Human Nutrition
Contact: kloboves@msu.edu
Cooperating Doctoral Program: Food Science & Human Nutrition
EITS Track: Food Toxicology & Ingredient Safety Track
Education: B.S. Public Health and Agronomy, National Taiwan University
Research Interests:
I have a great interest in studying the global risk assessment of mycotoxins, especially aflatoxin, among different countries. I am currently working with Dr. Felicia Wu on a project called, “Aflatoxin M1 Health Risks vs. Benefits of Dairy Consumption in Ethiopian Children: An Epidemiological Trial and Risk-Benefit Analysis.” In this project, our goal is to provide sound risk and epidemiological science to the question of aflatoxin M1 (AFM1) in dairy products: what its true health effects are, how any health risks compare to the nutritional benefits of milk
consumption, and what the implications are for rational policymaking. Moreover, we hope to fill gaps in knowledge and policy surrounding aflatoxin M1.
Additionally, my other research focus, “Sustainable, Systems-Based Solutions for Ensuring Low-Moisture Food Safety”, is mainly focusing on dealing the food recall problems of pathogenic bacteria (Salmonella) in low-moisture foods (almonds and raw flour). Through this study, based on the previous food recall cases that have occurred in the United States, we expect that
food product recall cases could be reduced by the improved traceability system, which involved with optimisation and models development. Moreover, we hope to estimate the economic loss resulting from the recalls of these two food products, thereby preventing the food recalls from happening repeatedly in the future.
Major Professor: Felicia Wu, John A. Hannah Distinguished Professor, Department of Food Science and Human Nutrition, Department of Agricultural, Food, and Resource Economics
Contact: hsupin@msu.edu
Cooperating Doctoral Program: Food Science & Human Nutrition
EITS Track: Biomedical Toxicology Track
Education: B.S. Biology, Ripon College
Research Interests:
I am interested in understanding the extent to which pregnant women are exposed to various environmental chemicals through their diets, and how this exposure could impact their health and the health of their baby. Specifically, I am interested in studying the endocrine and metabolic health of women during pregnancy. To accomplish my research objectives, I will focus on expanding my expertise in both diet and environmental chemicals as determinants of pregnancy health. First, diet/nutrition is an important predictor of maternal and fetal health in pregnancy. Diet quality indices can be used to categorize whole diets rather than focusing on individual foods or nutrients, and this approach is more appropriate for understanding how diet impacts the health of pregnant women at the population level. Therefore, a major component of my training will focus on evaluating or developing pregnancy-specific diet quality indices to understand how whole diets impact the health of both mother and baby. Chemical exposures can occur through a variety of daily-use products, including but not limited to: makeup, personal hygiene products, and packaging. Food is one of these possible points of exposure, and more needs to be understood about the impacts of various chemicals in our food on the health of pregnant women. The class of chemicals known as endocrine disrupting chemicals (EDCs) is of particular concern, especially for expecting mothers, because pregnancy is a hormonally sensitive period. My research will also focus on understanding how EDCs impact pregnancy health/outcomes. Importantly, the ultimate goal will be to thoroughly evaluate the role of diet quality in predicting EDC exposure and to understand how this relationship contributes to pregnancy health.
Major Professor: Rita Strakovsky, Human Nutrition
Contact: morrkel@msu.edu
Cooperating Doctoral Program: Food Science & Human Nutrition
EITS Track: Food Toxicology & Ingredient Safety Track
Education: B.S. Food Science and Technology, Lilongwe University of Agriculture and Natural Resources, M.S. Food Science, Michigan State University
Research Interests:
My research interest is on the impact of dietary fiber chemical structure on its gastrointestinal fermentation and gut microbial community structure in humans. My interest is to assess the impact of polyphenolic compounds intrinsic to these fiber sources on their utilization, gut microbiome, and potential effects on the risk of chronic diseases such as cancer. Polysaccharides are polymeric molecules with long chains of monosaccharides units bound together by glycosidic linkages. They are mainly fermented by the large intestinal microbiota hence they play a role in improving the gut microbiome. This is important research due to its implications for human health and diseases, it will help us discover the strategies of promoting gut health, preventing diseases like obesity and many other things.
Major Professor: Leslie Bourquin, Food Science & Human Nutrition
Contact: mthikora@msu.edu
Cooperating Doctoral Program: Microbiology, Genetics & Immunology
EITS Track: Environmental Toxicology
Education: B.S. Molecular Genetics, University of Vermont
Research Interests:
My research in the Reguera lab investigates the mechanisms used by metal-reducing bacteria in the genus Geobacter to grow in environments impacted by metal contaminants. These bacteria show promise for clean-up efforts because they are able to grow and immobilize toxic metals and radionuclides. Furthermore, their growth and activity can be stimulated in situ by the addition of acetate, their preferred electron donor. My lab uses Geobacter sulfurreducens and other laboratory representatives of the environmental strains to gain fundamental insights into the physiological adaptations that allow these microbes to grow in the presence of metals at concentrations otherwise lethal to most other bacteria.
I am particularly interested in further characterizing the conductive protein appendages (Type IV pili) that Geobacter cells assemble on the cell surface to bind and reduce toxic metals. Studies with uranium demonstrated that the pili bind the uranyl cation and reductively precipitate it outside the cell, simultaneously preventing it from traversing the cell envelope and providing energy for growth. Previous studies in my lab purified the pili and demonstrated they are protein nanowires. The team also resolved the structure of a pilus fiber via molecular dynamics and identified surface ligands that could function as metal-binding motifs and reductive sites for uranium and other cationic metals such as cobalt, gold, and silver. Additionally, my lab developed computational tools to design recombinant versions of the nanowire peptide (pilin) and assembled them in vitro into protein fibers with the same conductive properties as the native counterparts.
My dissertation builds on these studies and aims to 1) resolve the structure of the conductive pili via cryo-electron microscopy (a collaboration with Dr. Kristin Parent in the department of Biochemistry and Molecular Biology) and 2) investigate the spectrum of metals that they can bind and reductively precipitate. I am particularly interested in cadmium (Cd), a metal contaminant that is persistent in agricultural soils and aquaculture systems. The solubility of the Cd2+ cation makes it highly mobile in soils and promotes its rapid uptake and concentration in plants, farmed animals, and shellfish. Cumulative exposure from these sources through dietary intake is prevalent and has long-term health consequences. Also of interest to food security is the fact that Cd, even when present in moderate and “safe” amounts, co-selects for metal and antibiotic resistance in foodborne pathogens. Cd also leaches rapidly in agricultural runoffs, increasing the risk of exposure and the selective pressure for “superbugs”. Yet Geobacter bacteria live in environments impacted by cadmium contamination, tolerate high concentrations of the mobile and toxic Cd2+. cation, and are known to contribute to its mineralization. This makes them great model systems to investigate how metal stressors contribute to the co-selection of antibiotic traits in microbial communities. Hence, my dissertation also includes a third aim that will investigate genomewide responses of Geobacter bacteria to Cd stress. The size, charge, and coordination of the pilus metal traps suggests that it can bind Cd2+, providing a biological mechanism for its reductive precipitation as Cd0. This reaction could help detoxify the metal, but it is at the thermodynamic edge and is therefore unlikely to generate energy for growth. Thus, yet unknown adaptive responses allow Geobacter cells to remain viable and metabolically active in environments impacted by Cd contamination.
Major Professor: Gemma Reguera, Microbiology and Molecular Genetics
Contact: clarkmo9@msu.edu
Cooperating Doctoral Program: Microbiology, Genetics & Immunology
EITS Track: Biomedical Toxicology
Education: B.S. Biochemistry, California State University, Northridge
Research Interests:
Dr. Pestka's lab research regarding silica exposure aligns with a personal experience. One of my family members was occupationally exposed to silica and developed fibrosis which ultimately led to his passing. Because of this, I am interested in the modulation of silica induced autoimmunity by lipidome modification. I hope to further investigate not only the development of silicosis but of lupus as well, the autoimmune disease of interest in the Pestka lab. I hope to do this by bulk RNA sequencing lung tissues from previous graduate students to measure gene expression of epithelial cells. I also hope to conduct both in vivo subchronic and acute silica exposure, looking at mRNA expression in the lung. To further characterize disease development, I am interested in using different alveolar macrophage and lupus prone mouse models, than what is currently used in the lab.
Major Professor: James Pestka, Food Science & Human Nutrition, Microbiology, Genetics & Immunology
Contact: estra100@msu.edu
Cooperating Doctoral Program: Microbiology, Genetics & Immunology
EITS Track: Biomedical Toxicology
Education: B.S. Biomedical Sciences, Western Michigan University
Research Interests:
With the implementation of combined antiretroviral therapy (cART) HIV prognosis has shifted to a manageable chronic disease. However, as this population of people with HIV age there is a correlated increasein neuroinflammation, which may contribute to the pathogenesis of HIV associated neurocognitive disorders (HAND). CD8+T cells are capable of crossing the blood brain barrier and potentially contribute to this inflammation. My project will assess the immunopharmacological nad immunotoxicological effects of cannabinoid treatment, specifically THC and JWH-015 (a selective CB2 agonist), on primary human CD8+T cells. Once the immunopharmacological/immunotoxicological effects of the cannabinoid treatment have been determined we will develop a coculture of primary human astrocytes with the cannabinoid treated primary human CD8+T cells.
Major Professor: Norbert Kaminski, Pharmacology & Toxicology
Contact: martyjoe@msu.edu
Cooperating Doctoral Program: Molecular, Cellular and Integrative Physiology
EITS Track: Biomedical Toxicology
Education: B.S. Microbiology, Michigan State University
Research Interests:
I have very diverse research interests, from XNAs (xenonucleic acids) in making artificial microbial genomes to designing novel therapeutics for human diseases, but I'll focus on my disseration topic. Autoimmune disease disproportionately affects women, but the environmental toxicants that trigger autoimmune flare-ups are generally occupational hazards in malebiased occupations: silicates & particulates (construction), UV light & pesticides/herbicides (agriculture), and smoke & industrial solvents (manufacturing). The discrepancy between this sex bias in disease and trigger reinforce the importance of genetics and sex hormones in the incidence of autoimmune disease, but may also hold key information in understanding the sex differences in immunity that drive autoimmune disease severity. If we treat autoimmune model mice with autoimmune flare-associated toxins, then they will show increased disease severity in a sex biased manner. To study this, I plan to use pristane-treated BALB/cJ and MRL/lpr mice to model autoimmunity, and then I will separate them by sex and treatment of one of the occupational toxicants. We're currently starting with glyphosate, the primary reagent in the herbicide, RoundUp, as it is quite ubiquitously used in American agriculture and has been linked with increased rates of Rheumatoid Arthritis in farmers who apply it. Following a 14-day oral gavage pretreatment with a chronic* 500mg/kg dose (*below the NOAEL limit of 885mg/kg for mice) starting when they are 6-8 weeks old, we will monitor the mice for the presence of autoantibodies in their serum, skin rashes, hunched back, decreased weight, and any other signs of autoimmune disease. We will sacrifice the mice at month 3 and evaluate their kidneys, spleen, plasma, brain, and other organs for disease. To do so, we plan to employ IHC/IF of inflammatory signals in kidney and other tissue slices, flow cytometry on blood immune cells, anti-nuclear antigen ELISA, and more to characterize the effect of the toxins on the disease. Further aims would repeat these experiments with different toxicants and frame the data against current policies and treatments for autoimmune patients.
Major Professor: Yun Liang, Physiology
Contact: kennico2@msu.edu
Cooperating Doctoral Program: Pharmacology & Toxicology
EITS Track: Biomedical Toxicology
Education: B.S. University of Detroit Mercy
Research Interests: Nuclear factor erythroid 2-related factor (Nrf2) is a transcription factor that helps regulate antioxidant proteins involved in protection against oxidative and inflammatory stress. Studies show that Nrf2 demonstrates anti-inflammatory effects and plays a key role in decreasing susceptibility to chronic illnesses related to oxidative stress, thus it has been a therapeutic target of interest for several diseases. Data from our lab suggests that Nrf2 modulates T cell activation and CD8+ T cell effector function. Specifically, our lab has demonstrated that tBHQ, a potent Nrf2 activator, blunts the expression of CD107, a marker of T cell degranulation, on CD8+ T cells, suggesting that it impedes T cell activation and suppresses effector function. Although published data from our lab demonstrates a T cell autonomous role for Nrf2 in modulating T cell function, there is considerable evidence from other labs to show that Nrf2 also regulates antigen-presenting cells, such as dendritic cells. Notably, Nrf2 has been shown to regulate the T cell response by modulating dendritic cell activation induced by oxidative stress. In addition, it has been shown that dendritic cells lacking Nrf2 demonstrate increased expression of MHC class II, and the co-stimulatory molecules CD86, and CD80, which work jointly to promote T cell responses. Our hypothesis is that Nrf2 activation by tBHQ in dendritic cells will inhibit expression of MHC class II and other co-stimulatory molecules involved in effector functions, suggesting a blunted immune response after influenza infection. I intend to test this hypothesis in our mouse model of influenza and through the use of Nrf2-deficient models. I am concurrently developing in vitro assays to complement our in vivo approach.
Major Professor: Cheryl Rockwell, Pharmacology and Toxicology
Contact: awalisaa@msu.edu
Cooperating Doctoral Program: Pharmacology & Toxicology
EITS Track: Food Toxicology & Ingredient Safety
Education: B.S. Nutrition and Biology, Morgan State University
Research Interests: My dissertation research will focus on characterizing exposure to PFAS chemicals and investigating impacts on immune function. I am currently involved with research that aims to quantify concentrations of PFAS in the body as well as in drinking water and other potential sources. Questionnaires are being administered to obtain information about participant demographics, diet, and habits. I will employ statistical models to determine relative contributions of exposure sources in relation to PFAS body burdens, and associations with measures of immune function. I will also use exposure models to reconstruct historic or current exposure from specific sources and calculate estimates of risk.
Major Professor: Courtney Carignan
Contact: bauerra2@msu.edu
Cooperating Doctoral Program: Pharmacology & Toxicology
EITS Track: Biomedical Toxicology
Education: B.S. Biochemistry, Michigan State University
Research Interests: Immunopharmacology/immunotoxicology of cannabinoids. Dissertation project will be in this general area, but the specific aims of the project will be determined in the near future.
Major Professor: Norbert Kaminski, Pharmacology & Toxicology
Contact: finnbri1@msu.edu
Cooperating Doctoral Program: Pharmacology & Toxicology
EITS Track: Biomedical Toxicology
Education: B.S. Natural Sciences with a concentration in Biology, University of Puerto Rico at Cayey
Research Interests: Liver health is profoundly influenced by hepatic immune homeostasis. Evidence suggests that dysregulation of the hepatic immune system aggravates liver disorders such as acute liver failure (ALF). ALF can arise as a consequence of acetaminophen (APAP) overdose, which is the most common cause of ALF in the United States. Recent data from our
laboratory demonstrate that after an initial hepatic insult by APAP, monocyte-derived macrophages (MDMs) are recruited to the site of injury where they initiate tissue repair. Under conditions of severe liver injury, however, MDMs become dysregulated and contribute to the progression of ALF. This results in the amplification of pro-inflammatory cytokines, including IL-6 and TNF alpha, which contribute to the systemic inflammation culminating in hepatic encephalopathy (HE; i.e., cognitive impairment) and multi-organ failure. The current treatment for APAP-induced hepatotoxicity is Nacetylcysteine (NAC). However, the efficacy of NAC is poor when administered beyond eight hours of APAP overdose. ALF patients often rely on liver transplantation (LT) as their only therapeutic option. LT may not be sufficient, however, if ALF patients present with severe HE. Despite the increasing knowledge in the field, the mechanisms whereby MDMs become dysregulated are incompletely understood. My research focuses on elucidating the mechanisms whereby MDMs become dysregulated and contribute to the sustained hepatic inflammation and HE in APAP-induced ALF. Understanding these mechanisms could provide critical insight into novel therapeutic targets to treat ALF patients.
Major Professor: Bryan Copple, Pharmacology & Toxicology
Contact: gonza737@msu.edu
Cooperating Doctoral Program: Pharmacology & Toxicology
EITS Track: Biomedical Toxicology
Education: B.S. Human Biology, Michigan State University
Research Interests: I am primarily interested in the links between inflammation and cancer. I am interested in how malignant cells and immune cells interact within the tumor microenvironment of lung, breast, and pancreatic cancer, and how we can modulate those interactions pharmacologically to help prevent or treat cancer. Currently, I am focusing on two targets for anti-cancer pharmacological intervention: the Nrf2 cytoprotective pathway and the RXR nuclear receptor.
Major Professor: Karen Liby, Pharmacology & Toxicology
Contact: moerlan2@msu.edu
Cooperating Doctoral Program: Pharmacology & Toxicology
EITS Track: Biomedical Toxicology
Education: B.S. Biochemistry, Marist College
Research Interests: I am extremely interested in understanding the mechanisms of toxicity of environmental contaminants and the role these toxicants may play in the promotion of cancer. The focus on my research is to understand the interaction of risk factors such as obesity and environmental exposures on multiple myleoma. Specifically, obesity has been associated with increased incidence and progression of multiple myeloma, as well as decreased survival rate. Additional, environmental exposures can also lead to similar poor outcomes. To understand why obesity causes a more aggresive outcome and worse survival rates, it is important to better understand the mechanisms of fat, specifically if factors secreted from fat contribute to worse myeloma progressions. Moreover, it also necessary to better understand if increased levels of fat can lead to different responses following different types of exposures, such as exposure to PFAS chemicals or Ahr ligands.
Major Professor: Jamie Bernard, Pharmacology & Toxicology
Contact: smusso@msu.edu
Cooperating Doctoral Program: Pharmacology & Toxicology
EITS Track: Biomedical Toxicology
Education: B.MLS. Medical Laboratory Science, University of Nigeria, Nsukka
Research Interests: My research interest is to elucidate the mechanism of chemical induced injury, and identify targeted treatment options.
Current study: Chloropicrin (Trichloronitromethane, CP), a toxic agent used during World War 1 as a warfare agent, is currently been used as a soil fumigant and pesticide. It is volatile and easily accessible, and this increases the probability of accidental and occupational exposure to CP, as well as its use in terrorism. Exposure to CP results in severe ocular injury, especially to the corneal. However, the mechanism of its injury is not well defined hence, treatment options are limited. Studies in our laboratory using human corneal epithelial (HCE) cells and ex vivo rabbit corneas suggests that GP-induced corneal pathogenesis is associated increased levels of nuclear erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (H0-1 ), a critical target enzyme downstream of Nrf2, suggesting that the Nrf2 pathway, a key antioxidant and cytoprotective system, could be activated following CP exposure. My current study in Dr. Neera Tewari-Singh's lab is focused on establishing an in vivo mouse ocular injury model with CP. I will further define the role of the Nrf2 pathway in GP-induced ocular injury using Nrf2 knockout (KO) mice. As part of our lab's novel therapeutic approach, I will be employing Nrf2 activators alone or in combination with SSOE in the treatment of GP-induced ocular injury. I propose that understanding the role of Nrf2 pathway in vivo is a critical first step in identifying targeted therapy.
Major Professor: Neera Tewari-Singh, Pharmacology & Toxicology
Contact: okoyeoch@msu.edu
Cooperating Doctoral Program: Pharmacology & Toxicology
EITS Track: Biomedical Toxicology
Education: B.S. Animal Science, Michigan State University; M.S. Comparative Medicine and Integrative Biology, Michigan State University
Research Interests: My research interests focus on the determining mechanisms of chemical warfare agent-induced toxicity and developing therapies for use in victims of chemical warfare agents. My dissertation research currently focuses on the role of mast cells in acute and long-term cutaneous and systemic injury arising from exposure to nitrogen mustard (NM), an analog of sulfur mustard (SM; the most widely used vesicating, or blister, agent).
Currently, my research focuses on examining the acute and long-term cutaneous and hematological effects of a single, topically applied dose of NM in C57BL/6 mice. The results of this study will lay the groundwork for further investigations using mast cell-deficient and Nrf2 knock-out mice to explore the roles of mast cells and the Nrf2 pathway, respectively, in NM-induced toxicity. The end goal of this research is to identify if masts and Nrf2 might be potential therapeutic targets for anti-NM/SM therapies and, if so, to identify practical therapies.
Major Professor: Neera Tewari-Singh, Pharmacology & Toxicology
Contact: roneyand@msu.edu
Cooperating Doctoral Program: Pharmacology & Toxicology
EITS Track: Biomedical Toxicology
Education: B.S. Clinical and Applied Health Sciences, Drake University
Research Interests:
My research interest is in computational cardiovascular safety pharmacology. Safety pharmacology is a subset of pharmacology specializing in detecting and investigating potential undesirable pharmacodynamic effects of new chemical entities on physiological functions in relation to exposure in the therapeutic range and beyond. It exists as the bridge between toxicology and pharmacology. Specifically, my dissertation aims to focus on the creation of a concentration-effect model of blood pressure in preclinical animal models. In 2018 the FDA released a draft clinical guidance proposing a new safety endpoint for consideration in drug development, increases in systolic blood pressure greater than 3mmHg. This guidance focuses on determining this effect in the clinical phases, and more specifically, in the patient population. However, due to the resource commitment of getting a molecule to clinical development, as well as the potential concern for determining drug toxicities directly in the patient population, it would be prudent to rule out such an effect in the preclinical.
Major Professor: Adam Lauver, Pharmacology & Toxicology
Contact: sadkokam@msu.edu
Cooperating Doctoral Program: Pharmacology and Toxicology
EITS Track: Biomedical Toxicology
Education: B.S. Neuroscience, Michigan State University
Research Interests:
With the development of anti-retroviral therapy (ART), HIV has become a more manageable disease. This new treatment has successfully extended the life expectancy of the those afflicted with HIV to a life span comparable to a healthy individual. However, new problems arise as individuals live longer with HIV, such as development of HIV-associated neurodegenerative disease (HAND). Today, many individuals with HIV use cannabis to cope with side effects associated with the ART drugs. Previous research in the literature has shown that individuals with HIV who use cannabis have a decreased incidence of HAND development. My research will focus on elucidating the molecular mechanism of how cannabinoids induce their immunotoxicological and immmunopharmacological effects on the human immune system in the context of HIV.
Major Professor: Norbert Kaminski, Pharmacology & Toxicology
Contact: sermetse@msu.edu
Cooperating Doctoral Program: Pharmacology and Toxicology
EITS Track: Biomedical Toxicology
Education: B.S. Biochemistry, Kwame Nkrumah University of Science and Technology
Research Interests:
Visceral obesity increases the risk for both pre- and post-menopausal estrogen receptor positive breast cancer and pre-menopausal triple negative breast cancer (TNBC), however the mechanism has not been fully elucidated. Moreover, TNBC is the most aggressive and difficult breast cancer type to treat, with no current means of prevention. Our laboratory’s previous studies demonstrated that fibroblast growth factor-2 (FGF2) is released from visceral adipose tissue
(VAT) and promotes mammary epithelial cell malignant transformation through the fibroblast growth factor-1 receptor (FGFR1). As part of my training in pharmacology and drug discovery, I worked with Bernard lab members to use our novel high throughput screen (HTS) to identify MSU generated terpenoids and cyclic peptides that inhibit FGF2-stimulated malignant transformation. These compounds were generated in collaboration with Drs. Richard Neubig, Edmund Elsworth, Johnathan Walton and Bjoern Hamberger (MSU). In this unique chemoprevention HTS,
non-tumorigenic cells are stimulated to undergo anchorage-independent growth, a model of malignant transformation. Using this platform and anchorage-independent growth in soft agar, I confirmed that four terpenoids prevented FGF2-stimulated transformation. I propose to narrow down compounds based upon safety and efficacy and test these natural products in vivo as chemopreventive agents. Moreover, I wish to understand their mechanisms of action. I hypothesize that VAT secretes FGF2 and induces downstream signaling driving mammary carcinogenesis and this can be prevented with natural products. This project will take the early steps to identify chemopreventive agents against breast cancer when VAT is a threatening risk factor.
Major Professor: Jamie Bernard, Pharmacology and Toxicology
Contact: yawsonna@msu.edu
Cooperating Doctoral Program: Plant, Soil and Microbial Sciences
EITS Track: Environmental Toxicology
Education: B.S. Chemistry, George Mason University
Research Interests: I am researching the interactions of prions with geosorbents and heavy metals in order to better understand prion protein interactions and their fate in the environment and possible methods of remediation. Prions are infectious proteinaceous particles that are the sole agent of transmissible spongiform encephalopathies including mad cow disease, scrapie in sheep, and chronic wasting disease (CWD) in deer and other cervids. Prions can survive for years in the environment and remain infectious, and horizontal transmission of CWD through prions in soil, water, plant surfaces, and other matrices, is significant. One primary goal of my research is to explore the possibility that biochar and other carbon materials can serve as effective sorbents of prions, which could reduce their biovailability. To accomplish this, I am using computational simulations (molecular dynamics) to study the mechanisms of adsorption of prions to graphene (a model carbon surface) and binding strength. I also plan on comparing prion sorption to graphene and clay in order to assess how competitively carbon materials can bind prions in a soil environment. The second primary goal of my research is to study prion interactions with heavy metals, especially copper, which is known to interact with the prion protein. So far, I have conducted molecular dynamics simulations studying the binding sites of copper to the prion protein structure and conformational changes that occur due to copper binding.
Major Professor: Wei Zhang, Plant, Soil and Microbial Sciences
Contact: benedi89@msu.edu
Cooperating Doctoral Program: Plant, Soil and Microbial Sciences
EITS Track: Environmental Toxicology
Education: B.S. Environmental Microbiology
Research Interests: My research interest focuses on crop uptake of metal(loids) from soils as influenced by soil conditions and agricultural practices. While some metal(loids) such as lead (Pb), arsenic (As), cadmium (Cd), and chromium (Cr) are toxic to humans, some metal(loids) are essential to human health as appropriate dosage levels, including copper (Cu), manganese (Mn), zinc (Zn), and selenium (Se). My research aims to identify soil amendments that can decrease the crop uptake of toxic metal(loids) without jeopardizing the crop uptake of essential metal(loids). Further, I will use engineered nanomaterials such as sulfur nanoparticles and hydroxyapatite nanoparticles as soil amendments to decrease the crop uptake of toxic metal(loids). Finally, I will study how microbial communities and plant-microbe interactions contribute to the crop uptake of metal(loids) using culturing, genomic, and transcriptomic approaches The overall goal of my research is to promote the production of safe, nutritional crops using environmentally friendly and sustainable practices.
Major Professor: Wei Zhang, Plant, Soil and Microbial Sciences
Contact: lichenx1@msu.edu
Cooperating Doctoral Program: Plant, Soil and Microbial Sciences
EITS Track: Environmental Toxicology
Education: B.S. Environmental Sciences / B.A. Chemistry, University of Iowa
Research Interests: My research program is to study uptake and accumulation of poly- and perfluoroalkyl substances (PFASs) and pharmaceuticals and personal care products (PPCPs) in the agricultural food crops. These emerging chemicals are frequently present in biosolids derived from wastewater treatment plants (WWTPs). The land application of biosolids to agricultural land as soil amendments and plant fertilizers could bring PFASs and PPCPs into soils, which could subsequently enter food crops and accumulate in the edible parts. Consumption of PFASs- and PPCPs-contaminated food crops can result in some adverse health problems to humans, especially to toddlers and children. Specific to my research, I will determine PFASs and PPCPs in biosolids samples collected from the WWTPs across the U.S., and achieved grain samples produced from the lands that had received the repeating applications of biosolids. In addition, I will conduct greenhouse experiments to examine how much PFASs and PPCPs will be accumulated in several agricultural food crops from the soils amended with biosolids. These research studies are essentially needed, because this information will be beneficial to estimating the health risk of humans after eating the crops grown in the biosolids-amended soils.
Major Professor: Hui Li, Plant, Soil and Microbial Sciences
Contact: xuzhilia@msu.edu